A pronounced decline in sleep occurs with aging. This deficit in sleep with aging presents a major problem for elderly individuals, causing daytime sleepiness and impairing alertness. However, the mechanism for this change in the sleep cycle with aging is not understood. In the previous cycle of this Program Project Grant, the hypothesis was explored that the deficit in sleep in aged individuals was due to a deterioration in the circadian pacemaker, i.e, suprachiasmatic nucleus (SCN). However, results from Czeisler's group indicate that older subjects show no change in period of the temperature rhythm. These findings raise the possibility that there is no change in the SCN's pacemaking ability, but that other coupling pathways might decline with age. One possibility is that homeostatic elements regulating sleep- wakefulness might be impaired with aging. Our studies will directly address the hypothesis that the defect in sleep caused by aging is a lack of responsiveness in the ventrolateral preoptic nucleus (VLPO) neurons to the accumulation of adenosine. Specific aim 1 will test the integrity of the VLPO neurons in young and old rats. We predict that in older animals for a given amount of prior wakefulness there is less c-fos expression in VLPO. This would indicate levels in VLPO neuron. We predict that for a given amount for prior wakefulness older rats will have less galanin mRNA levels in VLPO compared to young rats. Specific aim 2 will test the hypothesis that there may be reduced responsiveness of VLPO neurons to accumulation of adenosine because of a reduction in expression of adenosine receptors by VLPO neurons or their afferents during aging. Specific aim 3 will test the hypothesis that preoptic neurons themselves are hyporesponsive to adenosine in aged animals.